Patient-specific headset for diagnostic and therapeutic transcranial procedures

ABSTRACT

Systems, methods and devices are provided for performing diagnostic or therapeutic transcranial procedures using a patient-specific transcranial headset. The patient-specific headset may include a patient-specific frame that is fabricated, according to volumetric image data, to conform to an anatomical curvature of a portion of a patient&#39;s head. The patient-specific frame is configured to support a plurality of transducers in pre-selected positions and orientations, which may be spatially registered to the volumetric image data. This spatial registration may be employed to control at least a portion of the transducers to focus energy at a pre-selected tissue region.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims priority to U.S. Provisional Application No.62/298,873, titled “PATIENT-SPECIFIC HEADSET FOR DIAGNOSTIC ANDTHERAPEUTIC TRANSCRANIAL PROCEDURES” and filed on Feb. 23, 2016, theentire contents of which is incorporated herein by reference.

BACKGROUND

The present disclosure relates to transcranial diagnostic andtherapeutic procedures.

The application of focused ultrasound to the brain through the intactskull has a long history leading up to the clinical implementations ofthe present day. Since the first successful ablation of animal braintissue transcranially using a single transducer in 1980, to the presentday multi-center clinical trials of Magnetic Resonance (MR)-guidedfocused ultrasound for the treatment of essential tremor usinghemispherical phased arrays consisting of more than one thousandelements, new phased array designs have been conceptualized to overcomeprevious challenges, such as skull aberration correction, standing wavereduction, skull heating, and dual-frequency blood-brain barrierdisruption.

SUMMARY

Systems, methods and devices are provided for performing diagnostic ortherapeutic transcranial procedures using a patient-specifictranscranial headset. The patient-specific headset may include apatient-specific frame that is fabricated, according to volumetric imagedata, to conform to an anatomical curvature of a portion of a patient'shead. The patient-specific frame is configured to support a plurality oftransducers in pre-selected positions and orientations, which may bespatially registered to the volumetric image data. This spatialregistration may be employed to control at least a portion of thetransducers to focus energy at a pre-selected tissue region.

Accordingly, in a first aspect, there is provided a system forperforming diagnostic or therapeutic transcranial procedures, the systemcomprising:

a patient-specific transcranial headset comprising:

-   -   a patient-specific frame configured to conform to an anatomical        curvature of a portion of a patient's head, said        patient-specific frame having been fabricated based on        volumetric image data associated with the patient;    -   a plurality of transducers supported by said patient-specific        frame, wherein said plurality of transducers are supported in        pre-selected positions and orientations relative to said        patient-specific frame; and

control and processing hardware operably connected to said plurality oftransducers, wherein said control and processing hardware is configuredto:

-   -   obtain transducer registration data spatially registering the        pre-selected positions and orientations of said plurality of        transducers with the volumetric image data; and    -   control at least a portion of said plurality of transducers to        focus energy at a pre-selected tissue region.

In another aspect, there is provided a method of fabricating atranscranial headset for diagnostic or therapeutic procedures, themethod comprising:

obtaining, from volumetric image data of a patient's head, surface datacharacterizing an anatomical curvature of a portion of the patient'shead;

employing the surface data to generate a digital model of apatient-specific frame, such that the patient-specific frame conforms tothe anatomical curvature of the portion of the patient's head;

modifying the digital model such that the patient-specific framecomprises a plurality of transducer attachment interfaces for receivingand supporting a plurality of transducers in pre-selected positions andorientations relative to the patient's head;

fabricating the patient-specific frame according to the digital model;

securing the plurality of transducers to the transducer attachmentinterfaces; and

generating transducer registration data characterizing the positions andorientations of the plurality of transducers relative to the volumetricimage data.

In another aspect, there is provided a kit for performing diagnostic ortherapeutic transcranial procedures, the kit comprising:

a patient-specific transcranial headset comprising:

-   -   a patient-specific frame configured to conform to an anatomical        curvature of a portion of a patient's head, said        patient-specific frame having been fabricated based on        volumetric image data associated with the patient;    -   a plurality of transducers supported by said patient-specific        frame, wherein said plurality of transducers are supported in        pre-selected positions and orientations relative to said        patient-specific frame; and

transducer registration data spatially registering the pre-selectedpositions and orientations of said plurality of transducers with thevolumetric image data.

A further understanding of the functional and advantageous aspects ofthe disclosure can be realized by reference to the following detaileddescription and drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

Embodiments will now be described, by way of example only, withreference to the drawings, in which:

FIG. 1 shows a cross-sectional illustration of an examplepatient-specific headset for performing transcranial diagnostic and/ortherapeutic procedures.

FIG. 2 is a flow chart illustrating an example method of fabricating apatient-specific headset.

FIG. 3 shows a system for performing transcranial diagnostic and/ortherapeutic procedures.

FIG. 4 shows an example implementation of a patient-specific headsetthat includes a plurality of ultrasound modules, each module supportinga sub-array of phased-array ultrasound transducers.

FIG. 5A shows a photograph of an example ultrasound transducer module.

FIG. 5B shows a photograph of an example patient-specific headset,showing a plurality of ultrasound modules, each module supporting asub-array of phased-array ultrasound transducers.

FIG. 5C shows a photograph of an example patient-specific headset,showing a plurality of ultrasound modules connected to external drivingcircuiting via flexible cables.

DETAILED DESCRIPTION

Various embodiments and aspects of the disclosure will be described withreference to details discussed below. The following description anddrawings are illustrative of the disclosure and are not to be construedas limiting the disclosure. Numerous specific details are described toprovide a thorough understanding of various embodiments of the presentdisclosure. However, in certain instances, well-known or conventionaldetails are not described in order to provide a concise discussion ofembodiments of the present disclosure.

As used herein, the terms “comprises” and “comprising” are to beconstrued as being inclusive and open ended, and not exclusive.Specifically, when used in the specification and claims, the terms“comprises” and “comprising” and variations thereof mean the specifiedfeatures, steps or components are included. These terms are not to beinterpreted to exclude the presence of other features, steps orcomponents.

As used herein, the term “exemplary” means “serving as an example,instance, or illustration,” and should not be construed as preferred oradvantageous over other configurations disclosed herein.

As used herein, the terms “about” and “approximately” are meant to covervariations that may exist in the upper and lower limits of the ranges ofvalues, such as variations in properties, parameters, and dimensions.Unless otherwise specified, the terms “about” and “approximately” meanplus or minus 25 percent or less.

It is to be understood that unless otherwise specified, any specifiedrange or group is as a shorthand way of referring to each and everymember of a range or group individually, as well as each and everypossible sub-range or sub-group encompassed therein and similarly withrespect to any sub-ranges or sub-groups therein. Unless otherwisespecified, the present disclosure relates to and explicitly incorporateseach and every specific member and combination of sub-ranges orsub-groups.

As used herein, the term “on the order of”, when used in conjunctionwith a quantity or parameter, refers to a range spanning approximatelyone tenth to ten times the stated quantity or parameter.

Unless defined otherwise, all technical and scientific terms used hereinare intended to have the same meaning as commonly understood to one ofordinary skill in the art. Unless otherwise indicated, such as throughcontext, as used herein, the following terms are intended to have thefollowing meanings:

As used herein, the phrase “pre-operative” refers to an action, process,method, event or step that occurs or is carried out prior to a medicalprocedure. Pre-operative, as defined herein, is not limited to surgicalprocedures, and may refer to other types of medical procedures, such asdiagnostic and therapeutic procedures.

As used herein, the phrase “intraoperative” refers to an action,process, method, event or step that occurs or is carried out during atleast a portion of a medical procedure. Intraoperative, as definedherein, is not limited to surgical procedures, and may refer to othertypes of medical procedures, such as diagnostic and therapeuticprocedures.

Referring now to FIG. 1, a patient-specific headset 100 for performingtranscranial diagnostic or therapeutic procedures is shown worn on thehead 50 of a patient. The patient-specific headset 100, which includes apatient-specific frame (support structure) 110 that supports a pluralityof transducers 120, conforms to the anatomical contour of at least aportion of the patient's head. The patient-specific frame 110, which isshown in cross-section in FIG. 1, mechanically supports transducers 120in pre-selected positions and orientations. The transducers 120 may beused to transmit and/or receive energy for brain diagnostic ortherapeutic purposes or for localization of the skull surface.

The patient-specific frame 110 includes a plurality of attachmentinterfaces for receiving and supporting the transducers 120. In theexample embodiment shown in FIG. 1, the attachment interfaces areprovided as apertures (recesses) into which the transducers 120 areplaced. The transducers 120 may be affixed to the patient-specific frame110 according to a wide variety of different means, such as, but notlimited to, with an attachment mechanism (e.g. via fasteners that extendinto the patient-specific frame 110, optionally into pre-formed holes),or an adhesive such as a glue. In the example implementation shown inFIG. 1, the transducers 120 are remotely interfaced with electronicsthrough wires or through a flexible printed circuit board 140. Thetransducers 120 may be removably attachable to the patient-specificframe 110.

As shown in FIG. 1, the patient-specific headset may also include acoupling layer 130 that is provided adjacent to an inner surface of thepatient-specific frame. The outer surface of the coupling layer 130contacts distal surfaces of the transducers 120, and the inner surfaceof the coupling layer contacts the patient's head 50, therebyfacilitating coupling of energy between the transducers in thepatient-specific frame and the patient's head. The inclusion of thecoupling layer 130, and the composition and/or geometry of the couplinglayer, may be dependent on the type of transducers 120. For example, ifthe transducers 120 are ultrasound transducers, the coupling layer 130may be an acoustic coupling layer that facilitates propagation ofacoustic waves and reduces reflections at interfaces. In one exampleimplementation, the coupling layer 130 includes an elastic membrane thatretains a liquid layer between the transducer surfaces and the elasticmembrane, such that coupling to the skin is achieved.

Although FIG. 1 shows an example embodiment in which the transducers areultrasound transducers, it will be understood that the transducers maybe any transducers capable of emitting or receiving energy. Non-limitingexamples of different types of transducers include ultrasoundtransducers configured to emit and/or receive ultrasound energy,magnetic resonance coils (radio-frequency coils) and optical transducerssuch as lasers, light emitting diodes, and optical fibers coupled tosources and/or detectors. The transducers need not all be of the sametype, and a first portion of the transducers may be selected to emitand/or detect a first type of energy (e.g. ultrasound), and anotherportion of the transducers may be selected to emit and/or detect asecond type of energy (e.g. optical or electromagnetic waves).

In one example implementation, a first subset of the transducers may beultrasound transducers, and a second subset of the transducers may beoptical transducers (e.g. optical fibers in optical communication with asource and/or detector), such that the patient-specific headset iscapable of performing photoacoustic imaging.

In another example implementation, a first subset of the transducers maybe ultrasound transducers, and a second subset of the transducers may beMRI coils, such that the system is suitable for performing simultaneousultrasound and MR imaging or sonications while using MR imaging.

In another example implementation, a first subset of the transducers maybe MRI coils, and a second subset of the transducers may be positronemission detector (PET), such that the system is suitable for performingboth MR and PET imaging.

In another example implementation, a first subset of the transducers maybe MRI coils, and wherein a second subset of the transducers may bepositron emission detector (PET), and third subset of the transducersmay be ultrasound transducer, such that said system is suitable forperforming both MR and PET imaging while delivering ultrasound therapyor imaging.

In some example embodiments, at least a portion of the transducers aremay be transducer elements for forming a phased array (i.e. thetransducers may be phased-array transducers). Such phased-arraytransducers may be spatially arranged on the patient-specific headset toprovide a full phased array, or a sparse phased array.

In some example embodiments, the phased-array transducers may beprovided as a plurality of sub-arrays, where each sub-array ismechanically supported as a separate transducer module, such that eachtransducer module is mechanically supported on the patient-specificframe 110 by a respective attachment interface. For example, referringto FIG. 1, each transducer 120 may be a transducer module housing asub-array of transducers, such that the sub-arrays, spatiallydistributed on the patient-specific headset 100, separately formdistinct phased arrays, or collectively form a composite phased-array.The transducer modules, and their respective attachment interfaces, mayhave unique shapes (i.e. they may be respectively keyed), such that agiven transducer module fits uniquely with its respective attachmentinterface. If the phased array is formed by a set of transducer moduleshousing respective sub-arrays, the transducer modules may be spatiallydistributed on the patient-specific frame to reduce or minimize theformation of grating lobes.

As noted above, the patient-specific frame conforms to the anatomicalcontour of at least a portion of the patient's head. Such a conformalframe may be fabricated based on volumetric image data of the patient'shead. FIG. 2 illustrates an example method for fabricating apatient-specific frame based on volumetric image data associated withthe patient. In steps 200 and 210, volumetric image data of a patient'shead is obtained and processed to provide surface data characterizing ananatomical curvature (e.g. skin or bone surface) of a portion of thepatient's head. The volumetric data may be obtained, for example, byperforming imaging using an imaging modality such as, but not limitedto, magnetic resonance (MR) imaging and computed tomography (CT)imaging. The volumetric image data may be obtained based on a previouslyperformed imaging procedure.

The volumetric image data may be processed and segmented to obtainsurface data characterizing the surface of a portion of the patient'sskull. Such surface segmentation may be performed, for example, usingimaging processing software such as the Mimics™ software platform(Materialise, Belgium). Such software enables the creation of a 3D model(the surface data) of the surface of a portion of the patient's head.The model may be created using known techniques, such as using the stepsof thresholding, region growing and manual editing. Automaticthresholding may be performed to achieve a first approximation of thebony surfaces of the skull, followed by manual editing to obtain arefined model. Haptic modeling, for example using a modeling softwareplatform such as the PHANTOM™ Desktop Haptic Device, may be used tofurther refine the model. Additional example methods of image processingand segmentation of volumetric image data are disclosed in U.S. Pat. No.8,086,336.

Subsequently, as shown in step 220, the surface data is used to producea digital model of the patient-specific frame. For example, a suitablesoftware platform (such as the software package Surfacer™) may beemployed to generate a model based on a point cloud of surface datapoints. As shown at step 230, the model is then modified or refined(e.g. updated) to include a plurality of transducer attachmentinterfaces for receiving and supporting a plurality of transducers inpre-selected positions and orientations relative to the patient's head,and for supporting the transducers such that energy is coupledtranscranially.

The positions and orientations of the transducer attachment interfacesmay be selected, for example, to form one or more phased arrays oftransducers. In embodiments in which sub-arrays are formed by a set oftransducer modules housing respective sub-arrays, the transducer modulesmay be spatially distributed on the patient-specific frame to reduce orminimize the formation of grating lobes.

The digital model may be further refined to include one or moreadditional features, such as, but not limited to, an attachmentinterface for the attachment of one or more fiducial markers, anaperture to permit surgical access to a selected region of the patient'shead when the patient-specific frame is worn, markers for identifyingreference directions, and one or more positioning features such asexternal handles.

The digital model, updated to include the transducer attachmentinterfaces, is then employed to fabricate the patient-specific frame, asshown at step 240. For example, the patient-specific frame may befabricated from the model using 3D printing. In another example, themodel may be employed to produce a mold suitable for forming thepatient-specific frame, and the mold may be subsequently employed tofabricate the patient-specific frame.

After having fabricated the patient-specific frame, the transducers (ortransducer assemblies or modules) are secured (attached, adhered, etc.)to the respective transducer attachment interfaces of thepatient-specific frame, as shown at step 250.

In order to employ the patient-specific headset for performingdiagnostic or therapeutic procedures based on pre-operative volumetricimage data, a relationship may be established between the positions andorientations of the transducers and the volumetric image data (i.e. sothat both can be represented within a common reference frame).Accordingly, in step 260, the known positions and orientations of thetransducers (as prescribed in the digital model) are spatiallyregistered relative to the volumetric image data, thereby generatingtransducer registration data characterizing the positions andorientations of the transducers relative to the volumetric image data.For example, such transducer registration data may include the spatialcoordinates of the transducers, and vectors identifying their respectiveorientations, in the reference frame of the volumetric data. In anotherexample implementation, the transducer registration data may include acoordinate transformation for transforming the positions andorientations of the transducers from a first reference frame to thereference frame of the volumetric image data. The transducerregistration data enables the determination of the positions andorientations of the transducers relative to the volumetric image data,enabling, for example, the determination of suitable beamformingparameters to pulse one or more phased arrays (e.g. sub-arrays) oftransducers to focus an energy beam at a specific location or regionwithin the patient's head.

In some example embodiments, a subset of transducers may be configuredto emit an energy beam toward the skull of the patient and to detectenergy that is reflected from the skull in order to facilitate thedetection, for each transducer in the subset of transducers, of a localspatial offset of the skull of the patient relative to thepatient-specific frame. The detected spatial offsets may then beemployed to correct a spatial registration of the transducers relativeto the patient anatomy (e.g. the skull and/or one or more internaltissue regions of interest) or to perform corrections based on thedetected signals, for example, as disclosed in U.S. Pat. No. 6,612,988.For example, the subset of transducers may be ultrasound transducers,or, for example, optical fibers operably connected to an opticalcoherence tomography system.

In another embodiment, the registration between the headset and the headand brain can be achieved by performing imaging (for example MRI, CT,thomosynthesis, or x-ray) with the headset placed on the subjects head,allowing the transducer locations to be determined from the imagingvisible fiducial markers in the headset.

FIG. 3 provides a block diagram illustrating an example implementationof a system for performing diagnostic or therapeutic transcranialprocedures. Control and processing hardware 300 is operably connected tothe patient-specific transcranial headset 100, optionally via transducerdriver electronics/circuitry 380.

The control and processing hardware 300, which includes one or moreprocessors 310 (for example, a CPU/microprocessor), bus 305, memory 315,which may include random access memory (RAM) and/or read only memory(ROM), a data acquisition interface 320, a display 325, external storage330, one more communications interfaces 335, a power supply 340, and oneor more input/output devices and/or interfaces 345 (e.g. a speaker, auser input device, such as a keyboard, a keypad, a mouse, a positiontracked stylus, a position tracked probe, a foot switch, and/or amicrophone for capturing speech commands).

Volumetric image data 370 and transducer registration data 375 may bestored on an external database or stored in memory 315 or storage 330 ofcontrol and processing hardware 300.

The tracking system 365 may optionally be employed to track the positionand orientation of the patient, via detection of one or more fiducialmarkers 160 attached to the patient-specific headset 100, and optionallyone or more medical instruments or devices also having fiducial markersattached thereto. For example, passive or active signals emitted fromthe fiducial markers may be detected by a stereographic tracking systememploying two tracking cameras. The transducer drivingelectronics/circuitry 380 may include, for example, but is not limitedto, Tx/Rx switches, transmit and/or receive beamformers.

The control and processing hardware 300 may be programmed with programs,subroutines, applications or modules 350, which include executableinstructions, which when executed by the one or more processors 310,causes the system to perform one or more methods described in thepresent disclosure. Such instructions may be stored, for example, inmemory 315 and/or other storage.

In the example embodiment shown, the transducer control module 355includes executable instructions for controlling the transducers of thepatient-specific transcranial headset 100 to deliver energy to a targetlocation or region of interest, based on the registration of thetransducer positions and orientations with the volumetric image data asper the transducer registration data 375. For example, thepatient-specific headset 100 may support a plurality of phased-arraytransducers, and transducer control module 355 may control thebeamforming applied (on transmit and/or receive) to deliver, based onthe known positions and orientations of the phased array transducersrelative to the volumetric image data, one or more focused energy beamsto a region of interest. The region of interest may be specifiedintraoperatively by a user (e.g. via a user interface controlled bycontrol and processing hardware 300) or according to a pre-establishedsurgical plan.

The registration module 360 may optionally be employed for registeringvolumetric image data 370 to an intraoperative reference frameassociated with tracking system 365. The optional guidance userinterface module 362 includes executable instructions for displaying auser interface showing spatially registered volumetric images forimage-guided procedures. The registration module 360 may alsointraoperatively receive spatial correction information based on adetected spatial offset between the patient-specific frame and thepatient's head (which, as described above, may be provided by a subsetof distance-sensing transducers) and employ this spatial correctioninformation to dynamically adjust (e.g. correct) the registrationbetween the transducers and the volumetric image data.

Although only one of each component is illustrated in FIG. 3, any numberof each component can be included in the control and processing hardware300. For example, a computer typically contains a number of differentdata storage media. Furthermore, although bus 305 is depicted as asingle connection between all of the components, it will be appreciatedthat the bus 305 may represent one or more circuits, devices orcommunication channels which link two or more of the components. Forexample, in personal computers, bus 305 often includes or is amotherboard. Control and processing hardware 300 may include many moreor less components than those shown.

The control and processing hardware 300 may be implemented as one ormore physical devices that are coupled to processor 310 through one ofmore communications channels or interfaces. For example, control andprocessing hardware 300 can be implemented using application specificintegrated circuits (ASICs). Alternatively, control and processinghardware 300 can be implemented as a combination of hardware andsoftware, where the software is loaded into the processor from thememory or over a network connection.

Some aspects of the present disclosure can be embodied, at least inpart, in software, which, when executed on a computing system,transforms a computing system into a specialty-purpose computing systemthat is capable of performing the methods disclosed herein. That is, thetechniques can be carried out in a computer system or other dataprocessing system in response to its processor, such as amicroprocessor, executing sequences of instructions contained in amemory, such as ROM, volatile RAM, non-volatile memory, cache, magneticand optical disks, or a remote storage device. Further, the instructionscan be downloaded into a computing device over a data network in a formof compiled and linked version. Alternatively, the logic to perform theprocesses as discussed above could be implemented in additional computerand/or machine readable media, such as discrete hardware components aslarge-scale integrated circuits (LSI's), application-specific integratedcircuits (ASIC's), or firmware such as electrically erasableprogrammable read-only memory (EEPROM's) and field-programmable gatearrays (FPGAs).

A computer readable medium can be used to store software and data whichwhen executed by a data processing system causes the system to performvarious methods. The executable software and data can be stored invarious places including for example ROM, volatile RAM, non-volatilememory and/or cache. Portions of this software and/or data can be storedin any one of these storage devices. In general, a machine readablemedium includes any mechanism that provides (i.e., stores and/ortransmits) information in a form accessible by a machine (e.g., acomputer, network device, personal digital assistant, manufacturingtool, any device with a set of one or more processors, etc.).

Examples of computer-readable media include but are not limited torecordable and non-recordable type media such as volatile andnon-volatile memory devices, read only memory (ROM), random accessmemory (RAM), flash memory devices, floppy and other removable disks,magnetic disk storage media, optical storage media (e.g., compact discs(CDs),digital versatile disks (DVDs), etc.), among others. Theinstructions can be embodied in digital and analog communication linksfor electrical, optical, acoustical or other forms of propagatedsignals, such as carrier waves, infrared signals, digital signals, andthe like. As used herein, the phrases “computer readable material” and“computer readable storage medium” refer to all computer-readable media,except for a transitory propagating signal per se.

The patient-specific headset and associated transducer registration datamay be employed for a wide variety of transcranial procedures,including, but not limited to, neuromodulation, neurostimulation,neuroimaging, neuro-monitoring, focused-ultrasound transcranialablation, mild heating (hyperthermia), neuromodulation,neurostimulation, mechanical excitation of the brain for diagnostic ortherapeutic purposes, manipulation, control, excitation or sensing ofgas bubbles, liquid droplets, solid particles, cells, nanoparticles,quantum dots or electronic circuits or devices, focused-ultrasoundtranscranial excitation or sensing of brain implants, devices,electronic circuits or sensors and transcranial procedures involving theuse of focused ultrasound to disruption and opening of the blood-brainbarrier for delivery of therapeutic or diagnostic agents, cells,particles, droplets, bubbles, electronic devices, transmitters, sensorsor other foreign material for diagnostic purposes.

It will be understood that although the present disclosure includes manyexample embodiments pertaining to a patient-specific headset that is tobe worn on the patient's head, the systems, devices and method disclosedherein may be adapted to provide a patient-specific apparatus forperforming diagnostic or therapeutic procedures on other parts orportions of the body. The patient-specific frame may be fabricatedaccording to volumetric image data of other body regions or bodyportions. For example, a patient-specific frame may be fabricated, basedon volumetric image data of a patient's knee, such that thepatient-specific frame conforms to the contour of the patient's knee,for performing a diagnostic or therapeutic procedure on the knee usingthe transducer supported by the patient-specific frame. Similarly, apatient-specific frame may be fabricated, based on volumetric image dataof a patient's spine, such that the patient-specific frame conforms tothe contour of the patient's spine, for performing a diagnostic ortherapeutic procedure on the spine using the transducer supported by thepatient-specific frame.

EXAMPLES

The following examples are presented to enable those skilled in the artto understand and to practice embodiments of the present disclosure.They should not be considered as a limitation on the scope of thedisclosure, but merely as being illustrative and representative thereof.

Referring now to FIG. 4, an example patient-specific headset 400 isshown, where the patient specific frame 410 (sub-array holder) supportsa plurality of focused ultrasound phased array transducers. This examplesystem may be employed, for example, for neuromodulation experiments ortreatments in humans or large animals.

As shown in FIG. 4, ultrasound beams 420 are generated by multipletransducer sub-array modules 430, where each transducer sub-array moduleincludes, in one example implementation, a set of 64 transducer elementsspaced at the center-to-center distance of half-wavelength, makingcomplete electronic beam steering possible. For example, at anultrasound frequency of 500 kHz, the module size of the aforementionedexample implementation would be approximately 8.5 mm×8.5 mm, but willscale inversely with frequency. Larger center-to-center spacing could beused by limiting the steering range, accepting some grating lobes, or bymaking the array surface curved such that it and only steering the arrayfocus to a limited volume of tissue. Each of the modules may beconnected to a 64-channel RF-driving board via a flex circuit. Aphotograph of an example of such a sub-array module is shown in FIG. 5A.FIGS. 5B and 5C shows an image of a plurality of sub-modules assembledand supported on a patient-specific frame.

In one example implementation, the aforementioned modules may beprovided as sub-modules 440 that form a sub-array module 430 connectedto a rigid base that will support and hold the module in place. Eachsub-array module 430 may also house one or more (e.g. four)PVDF-wideband receivers 450 to detect reflections from the skullsurfaces and scattering from the brain tissue. The location and numberof these modules may be selected, on a per-patient basis, based oncomputer simulations, such that they all form a sparse (e.g. optimal)array where the distances between the modules have suitable (e.g.maximal) variability to prevent grating lobe formation.

As noted above, the computer simulations employ volumetric image data(e.g. MRI or CT-scans) of the subject's head to obtain a model of thesurface of the patient's head, and to perform the calculations of thespatial distribution of the transducers modules relative to the patientanatomy. This information may be used with a 3D-printer to form aplastic support (frame) that fits snugly over the subject's head, like acustom helmet that has mounting holes for the insertion of thesub-arrays. The sub-arrays may have unique shapes, so they would fitonly in the locations determined by the computer plan.

In the present example implementation, high-frequency transmit-receiveelements are also integrated in the sub-array assemblies (e.g. 128high-frequency elements), which can be used to determine the distance ofthe skull from the array. As noted above, such distances can be used toimprove the registration of previously obtained volumetric imaging datato the array co-ordinates, and potential avoiding the need foradditional intraoperative imaging. These high-frequency elements can beused continuously to track any head motion, and thus, there is no needfor invasive pin fixation, as is the case with the current devices.

As described above with reference to FIG. 1, an elastic membrane may beprovided that secures a liquid layer between the module surfaces and themembrane, thereby facilitating coupling to the skin when thepatient-specific headset is worn.

It is expected that a headset fabricated according to the designdescribed in the present example may be capable of driving 256sub-arrays, resulting in an array of over 16,000 individual elements and64 modules, although fewer elements may be required if adequate focusingcan be achieved. The maximal area of human skull cap that can be used topropagate ultrasound is expected to vary approximately between 450 and700 cm²; thus, the complete array may not be fully populated, and mayinstead be sparse, which still maintains the high focus quality with thecost of increased power requirements. It is expected that such sparsearray implementations will be compatible with all of the applications,which typically require low power during exposures (for example, such asopening of the blood-brain barrier and neuromodulation).

The specific embodiments described above have been shown by way ofexample, and it should be understood that these embodiments may besusceptible to various modifications and alternative forms. It should befurther understood that the claims are not intended to be limited to theparticular forms disclosed, but rather to cover all modifications,equivalents, and alternatives falling within the spirit and scope ofthis disclosure.

1. A system for performing diagnostic or therapeutic transcranial procedures, the system comprising: a patient-specific transcranial headset comprising: a patient-specific frame configured to conform to an anatomical curvature of a portion of a patient's head, said patient-specific frame having been fabricated based on volumetric image data associated with the patient; a plurality of transducers supported by said patient-specific frame, wherein said plurality of transducers are supported in pre-selected positions and orientations relative to said patient-specific frame; and control and processing hardware operably connected to said plurality of transducers, wherein said control and processing hardware is configured to: obtain transducer registration data spatially registering the pre-selected positions and orientations of said plurality of transducers with the volumetric image data; and control at least a portion of said plurality of transducers to focus energy at a pre-selected tissue region.
 2. The system according to claim 1 wherein at least a portion of said plurality of transducers are phased-array transducers.
 3. The system according to claim 2 wherein at least a portion of said phased-array transducers are ultrasound transducers.
 4. The system according to claim 3 wherein said phased-array transducers form a sparse array.
 5. The system according to claim 2 wherein at least a portion of said phased-array transducers are magnetic resonance coils.
 6. The system according to claim 1 wherein a first portion of said plurality of transducers are ultrasound transducers, and wherein a second portion of said plurality of transducers are optical transducers, such that said system is suitable for performing photoacoustic detection.
 7. The system according to claim 1 wherein a first portion of said plurality of transducers are ultrasound transducers, and wherein a second portion of said plurality of transducers are MRI coils, such that said system is suitable for performing simultaneous ultrasound and MR imaging or sonications while using MR imaging.
 8. The system according to claim 1 wherein a first portion of said plurality of transducers are MRI coils, and wherein a second portion of said plurality of transducers are positron emission detectors (PET), such that said system is suitable for performing both MR and PET imaging.
 9. The system according to claim 1 wherein a first portion of said plurality of transducers are MRI coils, and wherein a second portion of said plurality of transducers are positron emission detectors (PET), and third portion of said plurality of transducers are ultrasound transducer such that said system is suitable for performing both MR and PET imaging while delivering ultrasound therapy or imaging.
 10. The system according to claim 1 wherein said control and processing hardware is further configured to: control a subset of said plurality of transducers to measure, for each transducer of said subset of transducers, a spatial offset of the skull of the patient relative to said patient-specific frame; and employ the spatial offsets to correct a spatial registration of said plurality of transducers relative to the pre-selected tissue region.
 11. The system according to claim 10 wherein at least a portion of said subset of said plurality of transducers are ultrasound transducers.
 12. The system according to claim 10 wherein at least a portion of said subset of said plurality of transducers are optical fibers operably connected to an optical coherence tomography system.
 13. The system according to claim 1 wherein said patient-specific frame comprises a plastic support that conforms to the anatomical curvature of the portion of the patient's head.
 14. The system according to claim 13 wherein said plastic support comprises attachment interfaces formed therein for receiving and securing said plurality of transducers.
 15. The system according to claim 14 wherein each attachment interface is configured to receive and support a transducer module comprising a sub-array of transducers.
 16. The system according to claim 15 wherein each attachment interface and each transducer module have unique shapes, such that a given transducer module fits uniquely with its respective attachment interface.
 17. The system according to claim 15 wherein each sub-array comprises transducer elements for forming a phased array.
 18. The system according to claim 17 wherein each sub-array comprises a plurality of ultrasound transducer elements suitable for generating a focused ultrasound beam.
 19. The system according to claim 18 wherein the pre-selected positions and orientations of said attachment interfaces are selected to reduce grating lobes.
 20. The system according to claim 17 wherein each transducer module further comprises at least one imaging transducer configured to receive reflections from the patient's skull.
 21. The system according to claim 14 wherein said attachment interfaces comprise a plurality of recesses for receiving said plurality of transducers.
 22. The system according to claim 1 wherein said patient-specific transcranial headset further comprises a coupling layer, wherein said coupling layer is provided adjacent to an inner surface of said patient-specific frame such that when said patient-specific transcranial headset is worn, an outer surface of said coupling layer contacts distal surfaces of said plurality of transducers, and an inner surface of said coupling layer contacts the patient's head, thereby facilitating coupling of energy between said patient-specific frame and the patient's head.
 23. The system according to claim 1 wherein said patient-specific frame further comprises one or more fiducial markers attached thereto, and wherein said system further comprises: a tracking system configured to detect signals from said fiducial markers and determine a spatial position and orientation of said patient-specific frame within an intraoperative reference frame; and a navigation system configured to employ said spatial position and orientation of said patient-specific frame for generating and displaying navigation images.
 24. The system according to claim 1 wherein said transducers are removable.
 25. A method of fabricating a transcranial headset for diagnostic or therapeutic procedures, the method comprising: obtaining, from volumetric image data of a patient's head, surface data characterizing an anatomical curvature of a portion of the patient's head; employing the surface data to generate a digital model of a patient-specific frame, such that the patient-specific frame conforms to the anatomical curvature of the portion of the patient's head; modifying the digital model such that the patient-specific frame comprises a plurality of transducer attachment interfaces for receiving and supporting a plurality of transducers in pre-selected positions and orientations relative to the patient's head; fabricating the patient-specific frame according to the digital model; securing the plurality of transducers to the transducer attachment interfaces; and generating transducer registration data characterizing the positions and orientations of the plurality of transducers relative to the volumetric image data.
 26. The method according to claim 25 wherein fabricating the patient-specific frame comprises 3D printing the patient-specific frame.
 27. The method according to claim 25 wherein fabricating the patient-specific frame comprises fabricating a mold and employing the mold to fabricate the patient-specific frame.
 28. The method according to claim 25 wherein at least a portion of the transducers are phased-array ultrasound transducers, and wherein the pre-selected positions and orientations of the transducer attachment interfaces associated with the phased-array ultrasound transducers are selected to reduce grating lobes.
 29. A kit for performing diagnostic or therapeutic transcranial procedures, the kit comprising: a patient-specific transcranial headset comprising: a patient-specific frame configured to conform to an anatomical curvature of a portion of a patient's head, said patient-specific frame having been fabricated based on volumetric image data associated with the patient; a plurality of transducers supported by said patient-specific frame, wherein said plurality of transducers are supported in pre-selected positions and orientations relative to said patient-specific frame; and transducer registration data spatially registering the pre-selected positions and orientations of said plurality of transducers with the volumetric image data.
 30. The kit according to claim 29 wherein at least a portion of said plurality of transducers are phased-array transducers.
 31. The kit according to claim 30 wherein at least a portion of said phased-array transducers are ultrasound transducers.
 32. The kit according to claim 31 wherein said phased-array transducers form a sparse array.
 33. The kit according to claim 30 wherein at least a portion of said phased-array transducers are magnetic resonance coils.
 34. The kit according to claim 29 wherein a first portion of said plurality of transducers are ultrasound transducers, and wherein a second portion of said plurality of transducers are optical transducers.
 35. The kit according to claim 29 wherein a first portion of said plurality of transducers are ultrasound transducers, and wherein a second portion of said plurality of transducers are MRI coils, such that said patient-specific transcranial headset is suitable for performing simultaneous ultrasound and MR imaging or sonications while using MR imaging.
 36. The kit according to claim 29 wherein a first portion of said plurality of transducers are MRI coils, and wherein a second portion of said plurality of transducers are positron emission detectors (PET), such that said patient-specific transcranial headset is suitable for performing both MR and PET imaging.
 37. The kit according to claim 29 wherein a first portion of said plurality of transducers are MRI coils, and wherein a second portion of said plurality of transducers are positron emission detectors (PET), and third portion of said plurality of transducers are ultrasound transducer such that said patient-specific transcranial headset is suitable for performing both MR and PET imaging while delivering ultrasound therapy or imaging.
 38. The kit according to claim 29 wherein a subset of said plurality of transducers are configured to measure, for each transducer of said subset of transducers, a spatial offset of the skull of the patient relative to said patient-specific frame.
 39. The kit according to claim 38 wherein at least a portion of said subset of said plurality of transducers are ultrasound transducers.
 40. The kit according to claim 38 wherein at least a portion of said subset of said plurality of transducers are optical fibers operably connected to an optical coherence tomography system.
 41. The kit according to claim 29 wherein said patient-specific frame comprises a plastic support that conforms to the anatomical curvature of the portion of the patient's head.
 42. The kit according to claim 41 wherein said plastic support comprises attachment interfaces formed therein for receiving and securing said plurality of transducers.
 43. The kit according to claim 42 wherein each attachment interface is configured to receive and support a transducer module comprising a sub-array of transducers.
 44. The kit according to claim 43 wherein each attachment interface and each transducer module have unique shapes, such that a given transducer module fits uniquely with its respective attachment interface.
 45. The kit according to claim 43 wherein each sub-array comprises transducer elements for forming a phased array.
 46. The kit according to claim 43 wherein each sub-array comprises a plurality of ultrasound transducer elements suitable for generating a focused ultrasound beam.
 47. The kit according to claim 46 wherein the pre-selected positions and orientations of the attachment interfaces are selected to reduce grating lobes.
 48. The kit according to claim 46 wherein each transducer module further comprises at least one imaging transducer configured to receive reflections from the patient's skull.
 49. The kit according to claim 42 wherein said attachment interfaces comprise a plurality of recesses for receiving the plurality of transducers.
 50. The kit according to claim 29 wherein said patient-specific frame further comprises one or more fiducial markers attached thereto.
 51. The kit according to claim 29 wherein said transducers are removable. 